Polyarteritis Nodosa - PAN

Polyarteritis nodosa (PAN) is a necrotizing vasculitis resulting in aneurysmal formation and organ infarction. It is categorized as a medium-vessel vasculitis (Chapel Hill, 2012).

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory Testing

Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
- CBC – rule out infection
- Urinalysis (UA) – hematuria, proteinuria, red blood cell casts
- C-reactive protein (CRP) – frequently elevated
  - Preferred test to detect inflammatory processes (Choosing Wisely: 20 Things Physicians and Patients Should Question, American Society for Clinical Pathology, 2017)
  - If CRP not available, order erythrocyte sedimentation rate (ESR)
Testing to consider to rule out other diagnoses
- Antineutrophil cystoplasmic antibodies (ANCA) – rarely positive, rule out ANCA-associated vasculitis
- Hepatitis B surface antigen – rule out concomitant chronic hepatitis
- Antinuclear antibodies (ANA) – rule out connective tissue diseases
- Antiglomerular basement membrane antibodies – rule out an antiglomerular basement membrane disease (anti-GBM)

Histology

Small- and medium-size artery necrotizing vasculitis with absence of glomerulonephritis
Arterioles, capillaries, and/or venules – most affected
Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls

Imaging Studies

Angiography – microaneurysms and stenoses of medium vessels.

Differential Diagnosis

Alport syndrome
Connective tissue diseases
Anti-GBM disease (Goodpasture syndrome)
Vasculitis – microscopic polyangiitis
Infection
- Mycobacterium tuberculosis
- Endocarditis
- Hepatitis B/hepatitis C
- Treponema pallidum
- Cytomegalovirus
- Epstein-Barr virus
- HIV
- Plasmodium spp
Cryoglobulinemia
Malignancy
- Lymphoma
- Plasma cell dyscrasias

Background

Epidemiology

Incidence –16-25/million for systemic vasculitis as a group (includes eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and granulomatosis with polyangiitis)
Age – peak onset in 50s
Sex – M:F, equal

Risk Factors

Chronic hepatitis B

Clinical Presentation

Constitutional – fever, malaise, weight loss, arthralgias
Cardiovascular – acute coronary syndrome
Dermatological – vascular purpura, livedo reticularis, lower extremity ulcers, subcutaneous ulcers
Gastrointestinal – nonspecific abdominal pain, gastrointestinal bleeding, bowel perforation
Neurological – mononeuropathy multiplex
Renal – renovascular hypertension, vascular nephropathy

Pediatrics

Epidemiology

Age – peak is 9-11 years
Sex – M<F, slight

Clinical Presentation

Tends to be a more limited disorder than in adults
Constitutional – fever, malaise, weight loss
Musculoskeletal – arthritis/arthralgia, myositis, myalgia
Renal – vascular hypertension, hematuria, proteinuria
Neurological – peripheral neuropathy
Gastrointestinal – nonspecific abdominal pain
Dermatological – livedo reticularis, skin nodules, skin infections

Indications for Testing

Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory Testing

Nonspecific testing
- CBC – anemia, leukocytosis, thrombocytoses
- C-reactive protein (CRP) – usually elevated
  - Preferred test to detect inflammatory processes (Choosing Wisely: 20 Things Physicians and Patients Should Question, American Society for Clinical Pathology, 2017)
  - If CRP not available, order erythrocyte sedimentation rate (ESR)
- Urinalysis (UA) – proteinuria, hematuria, red cell casts
- Electrolytes – increases in blood urea nitrogen (BUN)/creatinine not uncommon
Antineutrophil cystoplastic antibodies (ANCA) – rarely positive

Differential Diagnosis

Infection
Vasculitis
- Microscopic polyangiitis
- Kawasaki disease
- IgA vasculitis
Connective tissue diseases
Alport syndrome

ARUP Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use

Identify anemia, leukocytosis, and thrombocytoses

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Recommended Use

Screen for various metabolic and kidney disorders

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Recommended Use

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Recommended Use

Preferred reflex panel for managing patients with a known diagnosis of vasculitis; may be assistive in evaluating suspected vasculitis

For the workup of suspected vasculitis, the preferred panel is antineutrophil cystoplasmic antibodies (ANCA)-associated vasculitis profile (ANCA/MPO/PR-3) with reflex to ANCA titer

Panel includes ANCA, IgG; myeloperoxidase antibody; and serine protease 3 antibody

Reflex pattern – if screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089
Method: Qualitative Chemiluminescent Immunoassay

Recommended Use

Can be ordered as part of the acute hepatitis panel which includes hepatitis A virus (HAV) IgM, hepatitis B virus (HBV) core antibody IgM, HBV surface antigen (HBsAg), and hepatitis C virus (HCV) antibody; refer to acute hepatitis panel with reflex to HBsAg confirmation

Reflex pattern – if results for HBsAg screen are repeatedly reactive with an index value between 1.00 and 50.00, then HBsAg confirmation will be added

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

Aid in initial diagnosis of connective tissue disease

Detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells

Reflex pattern – if antinuclear antibodies (ANA) are detected by enzyme-linked immunosorbent assay (ELISA), then ANA by indirect fluorescent antibody (IFA) titer will be added

Limitations

Results are not disease specific

Lower sensitivity than ANA IFA for systemic autoimmune rheumatic diseases

Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

Recommended Use

Detect glomerular basement membrane (GBM) antibodies in suspected or established anti-GBM disease

May be useful for monitoring treatment response

Panel includes GBM antibody, IgG by multiplex bead assay and IFA

Follow-up

Positive result should be confirmed by renal biopsy

Medical Reviewers

Slev, Patricia R., PhD, Laboratory Section Chief, Immunology, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

References

Guidelines

Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010; 69(5): 798-806. PubMed
Ruperto N, Ozen S, Pistorio A, Dolezalova P, Brogan P, Cabral DA, Cuttica R, Khubchandani R, Lovell DJ, O'Neil KM, Quartier P, Ravelli A, Iusan SM, Filocamo G, Magalhães CS, Unsal E, Oliveira S, Bracaglia C, Bagga A, Stanevicha V, Manzoni SM, Pratsidou P, Lepore L, Espada G, Kone-Paut I, Paut IK, Zulian F, Barone P, Bircan Z, Maldonado Md, Russo R, Vilca I, Tullus K, Cimaz R, Horneff G, Anton J, Garay S, Nielsen S, Barbano G, Martini A, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Ann Rheum Dis. 2010; 69(5): 790-7. PubMed
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jun 2018]

General References

Harrold LR, Liu NY. Polyarteritis nodosa presenting as pancytopenia: case report and review of the literature. Rheumatol Int. 2008; 28(10): 1049-51. PubMed

Kallenberg CG. The last classification of vasculitis. Clin Rev Allergy Immunol. 2008; 35(1-2): 5-10. PubMed

Pettigrew D, Teuber SS, Gershwin E. Polyarteritis nodosa. Compr Ther. 2007; 33(3): 144-9. PubMed

Testing Algorithms

Vasculitis in Adults Testing Algorithm

Read more about Vasculitis in Adults Testing Algorithm

Vasculitis in Children Testing Algorithm

Read more about Vasculitis in Children Testing Algorithm

Content Review:

December 2017

Last Update: August 2018


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	Polyarteritis Nodosa - PAN. ARUP Consult^©. Retrieved October 15, 2018, from: https://arupconsult.com/content/polyarteritis-nodosa